Biomechanics of echothiophate-induced anatomic changes in monkey aqueous outflow system.

Cynomolgus monkeys underwent long-term topical treatment with echothiophate, echothiophate + atropine, or control solution. Echothiophate-treated eyes exhibited increased intraocular pressure, collapse and densification of the trabecular meshwork with accumulation of extracellular material in the cribriform region, alterations in the shape and orientation of Schlemm's canal and the ciliary muscle, and discontinuity between ciliary muscle bundles and trabecular beams. Atropine or ciliary muscle disinsertion with subsequent scar formation supporting the mesh posteriorly at least partially prevented these alterations. Only sometimes did discontinuing echothiophate treatment restore normal anatomy. Collectively, these findings indicate that the pathophysiology of structural alterations in the outflow apparatus induced by echothiophate is mediated at least in part by an anterior segment muscarinic receptor, involves mechanical factors and underperfusion of the meshwork, and does not involve any direct toxic effect of echothiophate.